tbuckley/cabot-search huggingface dataset:
Hot Gloved Finger Sign in Endobronchial Metastasis From Hepatocellular Carcinoma on FDG PET/CT
Authors: Jun Zhang, Aisheng Dong, Yang Wang
Journal: Clinical Nuclear Medicine (2022)

Abstract Endobronchial metastasis from hepatocellular carcinoma is exceedingly rare. We describe FDG PET/CT findings in a case with isolated endobronchial metastasis from hepatocellular carcinoma 13 years after hepatectomy. The endobronchial metastasis appeared as hypermetabolic branching tubular opacities, producing a hot gloved finger sign on FDG PET/CT. This case indicates that the hot gloved finger sign may be suggestive of extensive endobronchial growing of a malignant condition but not endobronchial mucoid plug.
68Ga-FAPI-04 PET/CT Versus 18F-FDG PET/CT in the Detection of Malignant Gastrointestinal Stromal Tumor
Authors: Zeyu Zhang, Hongyuan Jiang, Lu Zhang, Chao Cheng, Changjing Zuo
Journal: Clinical Nuclear Medicine (2022)

A 65-year-old man presented with abdominal bloating for approximately 4 weeks. After CT imaging, it was diagnosed as gastric carcinoma with hepatic metastasis. 68Ga-FAPI-04 PET/CT revealed much higher tumor-to-background contrast and more metastatic lesions compared with 18F-FDG PET/CT in this case. Following gastroscopy and pathological examination, the final diagnosis was malignant gastrointestinal stromal tumor. This case demonstrated that 68Ga-FAPI-04 PET/CT was more sensitive than 18F-FDG PET/CT for detecting primary and metastatic lesions in malignant gastrointestinal stromal tumor.
Identification of high-risk subjects in nonalcoholic fatty liver disease
Authors: Christiane Stern, Laurent Castera
Journal: Clinical and Molecular Hepatology (2022)

Non-alcoholic fatty liver disease (NAFLD) is becoming the most common liver disease worldwide, and its burden is expected to increase due to the growing epidemic of obesity and diabetes. The key challenge among NAFLD patients is to identify those with advanced fibrosis (F3F4), who are at high risk of developing complications and will benefit from specialized management and treatment with new pharmacotherapies when they are approved. Liver biopsy appears unrealistic and unsuitable in practice, given the large number of high-risk patients and its well-known limitations. Non-invasive sequential algorithms using fibrosis-4 index as first-line test, followed by vibration-controlled transient elastography or patented blood test, are the best strategy for case finding of high-risk subjects. In fact, they are now recommended by several international guidelines, and should be used and disseminated to increase awareness among physicians beyond liver clinics where most NAFLD patients are seen.
Nanoformulations targeting immune cells for cancer therapy: mRNA therapeutics
Authors: Wei Yang, Jianwei Cao, Hui Cheng, Liang Chen, Meihua Yu, Yu Chen, Xingang Cui
Journal: Bioactive Materials (2022)

The approved worldwide use of two messenger RNA (mRNA) vaccines (BNT162b2 and mRNA-1273) in late 2020 has proven the remarkable success of mRNA therapeutics together with lipid nanoformulation technology in protecting people against coronaviruses during COVID-19 pandemic. This unprecedented and exciting dual strategy with nanoformulations and mRNA therapeutics in play is believed to be a promising paradigm in targeted cancer immunotherapy in future. Recent advances in nanoformulation technologies play a prominent role in adapting mRNA platform in cancer treatment. In this review, we introduce the biologic principles and advancements of mRNA technology, and chemistry fundamentals of intriguing mRNA delivery nanoformulations. We discuss the latest promising nano-mRNA therapeutics for enhanced cancer immunotherapy by modulation of targeted specific subtypes of immune cells, such as dendritic cells (DCs) at peripheral lymphoid organs for initiating mRNA cancer vaccine-mediated antigen specific immunotherapy, and DCs, natural killer (NK) cells, cytotoxic T cells, or multiple immunosuppressive immune cells at tumor microenvironment (TME) for reversing immune evasion. We highlight the clinical progress of advanced nano-mRNA therapeutics in targeted cancer therapy and provide our perspectives on future directions of this transformative integrated technology toward clinical implementation.
Trifluridine–tipiracil plus bevacizumab versus capecitabine plus bevacizumab as first-line treatment for patients with metastatic colorectal cancer ineligible for intensive therapy (SOLSTICE): a randomised, open-label phase 3 study
Authors: Thierry André, Alfredo Falcone, Yaroslav Shparyk, Fedor Moiseenko, Eduardo Polo-Marques, Tibor Csöszi, Arinilda Campos-Bragagnoli, Gabor Liposits, Ewa Chmielowska, Paul Aubel, Lourdes Martín, Ronan Fougeray, Nadia Amellal, Mark P Saunders
Journal: The Lancet. Gastroenterology & hepatology (2022)
Selected Articles from This Issue
Journal: Clinical Cancer Research (2022)

Davis and colleagues report the first systematic assessment of the safety and pharmacokinetics of dual immune checkpoint inhibition with ipilimumab and nivolumab in pediatric, adolescent, and young adult patients with relapsed or refractory sarcoma.They establish a recommended phase II dose of nivolumab (3 mg/kg) plus ipilimumab (1 mg/kg) and found the combination to be generally well tolerated.In expanded phase II cohorts, the authors observed two sustained partial responses.They further demonstrate that increased ipilimumab dosing (3 mg/kg) in combination with nivolumab (1 mg/kg) carries higher toxicity without clinical benefit in this population.
Substituting racemic ionizable lipids with stereopure ionizable lipids can increase mRNA delivery
Authors: Alejandro J. Da Silva Sanchez, Kun Zhao, Sebastian G. Huayamares, Marine Z.C. Hatit, Melissa P. Lokugamage, David Loughrey, Curtis Dobrowolski, Shuaishuai Wang, Hyejin Kim, Kalina Paunovska, Yanina Kuzminich, James E. Dahlman
Journal: Journal of Controlled Release (2022)
The need for rehabilitation services in the WHO European Region is substantial and growing
Authors: Satish Mishra, Justine Gosling, Ariane Laplante-Lévesque, Tomas Zapata, Natasha Azzopardi Muscat
Journal: The Lancet Regional Health - Europe (2022)

The WHO European Region covers a vast geographical area from the Atlantic to the Pacific oceans and includes 53 diverse Member States, where there is large variation in the accessibility and quality of rehabilitation services.One commonality is the substantial need for rehabilitation.The recently published, first-of-its-kind document "The need for rehabilitation services in the WHO European Region" 1 presents data from the 2019 Global Burden of Diseases, Injuries, and Risk Factors Study. 2,3In the WHO European Region in 2019, 394 million people had a condition amendable to rehabilitation during its course.This represents more than two in five people.Fig. 1 depicts the conditions driving the need for rehabilitation in the Region.The report findings help dispel common misconceptions, for example, that rehabilitation is a disability-specific service needed by only a few, or a luxury service-that only the selected few can afford.WHO defines rehabilitation as a set of interventions designed to optimize functioning and reduce disability in individuals with health conditions in interaction with their environment. 4Rehabilitation addresses a person's limitations in everyday physical, mental, and social functioning due to ageing or a health condition, including disease (acute or chronic), disorder, injury or trauma. 4Rehabilitation might be needed by anyone, regardless of age, gender, or socio-economic status.An ageing population and the rise of noncommunicable diseases are two of the main drivers of the growing need for rehabilitation services.Good health and functional capability promote inclusion and supports participation, allowing children to learn and adults to earn, providing an escape from poverty and the basis for long-term and
Modification of the Early Gene Enhancer-promoter Improves the Oncolytic Potency of Adenovirus 11
Authors: Han Hsi Wong, Guozhong Jiang, Rathi Gangeswaran, Pengju Wang, Jiwei Wang, Ming Yuan, Hexiao Wang, Vipul Bhakta, Heike Müller, Nicholas R. Lemoine, Yaohe Wang
Journal: Molecular Therapy (2022)

(Molecular Therapy 20, 306–316; February 2012) In the originally published version of this article, mistakes were present in the Western blots of Figure 4d, including the identical PCNA bands for Ad11 hexon expression in Capan-2 and PC-3. The hexon bands for PC-3 were identical to those of Figure 6b when different blot results should have been presented. The error was due to the inclusion of incorrect scanned blots and their misarrangement in Figure 4d. The corrected Figure 4d is shown below. These corrections do not change the conclusions of the paper, and the authors apologize for this error.Figure 4d. Mechanisms involved in the attenuated oncolytic potency of adenovirus serotype 11 (Ad11) (corrected)View Large Image Figure ViewerDownload Hi-res image Download (PPT) Modification of the Early Gene Enhancer-promoter Improves the Oncolytic Potency of Adenovirus 11Wong et al.Molecular TherapyFebruary, 2012In BriefOncolytic adenoviruses based on serotype 5 (Ad5) have several shortcomings, including the downregulation of its receptor in cancer cells, high prevalence of neutralizing antibodies and hepatotoxicity. Another adenoviral serotype, Ad11, could overcome these obstacles. Here, we show that human cancer cell lines express higher levels of the Ad11 receptor CD46, resulting in much better infectivity than Ad5. Surprisingly, only 36% (9/25) of the cell lines were more sensitive to Ad11- than to Ad5-mediated cytotoxicity. Full-Text PDF Open Archive
The WHO European framework for action to achieve the highest attainable standard of health for persons with disabilities 2022–2030
Authors: Satish Mishra, Elena S. Rotarou, Carrie Beth Peterson, Dikaios Sakellariou, Natasha Azzopardi Muscat
Journal: The Lancet Regional Health - Europe (2022)

There are approximately 135 million persons with disabilities in the WHO European Region. In order to address health inequities experienced by this population, Member States and WHO/Europe developed the 'WHO European framework for action to achieve the highest attainable standard of health for persons with disabilities 2022-2030', in close cooperation with organisations of persons with disabilities. The Framework, with its accompanying Resolution, was adopted by all 53 Member States in September 2022. The Framework is aligned with the core priorities of the WHO European Programme of Work 2020-2025, that is, achieving universal health coverage, protecting against health emergencies, and promoting health and well-being. It consists of four objectives, 13 targets, and 20 indicators that act as measures of progress and success, and as drivers for policy action and a roadmap for Member States towards a disability-inclusive health sector. The Framework is expected to have a significant impact on the health and well-being of all in the Region, and especially persons with disabilities, as it will advance inclusive health systems across the Region. Inclusive health sectors will aid towards the achievement of the Sustainable Development Goals, the protection of the human rights of persons with disabilities, and the promotion of their health.
Common mechanisms in pediatric acute liver failure
Authors: Jake P. Mann, Dominic Lenz, Zania Stamataki, Deirdre Kelly
Journal: Trends in Molecular Medicine (2022)

Acute liver failure (ALF) is a rare but potentially fatal disease in children. The etiology is multifactorial, including infection, autoimmune, and genetic disorders, as well as indeterminate hepatitis, which has a higher requirement for liver transplantation. Activation of the innate and adaptive immune systems leads to hepatocyte-specific injury which is mitigated by T regulatory cell activation. Recovery of the native liver depends on activation of apoptotic and regenerative pathways, including the integrated stress response (ISR; e.g., PERK), p53, and HNF4α. Loss-of-function mutations in these pathways cause recurrent ALF in response to non-hepatotropic viruses. Deeper understanding of these mechanisms will lead to improved diagnosis, management, and outcomes for pediatric ALF.
Circulating microRNAs as emerging regulators of COVID-19
Authors: Yu Liang, Dan Fang, Xiaojun Gao, Xin Deng, Ni Chen, Jianbo Wu, Min Zeng, Mao Luo
Journal: Theranostics (2022)

Coronavirus disease 2019 , an infectious disease caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a global pandemic that has high incidence rates, spreads rapidly, and has caused more than 6.5 million deaths globally to date.Currently, several drugs have been used in the clinical treatment of COVID-19, including antivirals (e.g., molnupiravir, baricitinib, and remdesivir), monoclonal antibodies (e.g., etesevimab and tocilizumab), protease inhibitors (e.g., paxlovid), and glucocorticoids (e.g., dexamethasone).Increasing evidence suggests that circulating microRNAs (miRNAs) are important regulators of viral infection and antiviral immune responses, including the biological processes involved in regulating COVID-19 infection and subsequent complications.During viral infection, both viral genes and host cytokines regulate transcriptional and posttranscriptional steps affecting viral replication.Virus-encoded miRNAs are a component of the immune evasion repertoire and function by directly targeting immune functions.Moreover, several host circulating miRNAs can contribute to viral immune escape and play an antiviral role by not only promoting nonstructural protein (nsp) 10 expression in SARS coronavirus, but among others inhibiting NOD-like receptor pyrin domain-containing (NLRP) 3 and IL-1β transcription.Consequently, understanding the expression and mechanism of action of circulating miRNAs during SARS-CoV-2 infection will provide unexpected insights into circulating miRNA-based studies.In this review, we examined the recent progress of circulating miRNAs in the regulation of severe inflammatory response, immune dysfunction, and thrombosis caused by SARS-CoV-2 infection, discussed the mechanisms of action, and highlighted the therapeutic challenges involving miRNA and future research directions in the treatment of COVID-19.
Polymeric microneedles enable simultaneous delivery of cancer immunomodulatory drugs and detection of skin biomarkers
Authors: Pere Dosta, Núria Puigmal, Alexander M. Cryer, Alma L. Rodríguez, Ella Scott, Ralph Weissleder, Miles A. Miller, Natalie Artzi
Journal: Theranostics (2022)

Background: Immune-modulating therapies impart positive outcomes in a subpopulation of cancer patients.Improved delivery strategies and non-invasive monitoring of anti-tumor effects can help enhance those outcomes and understand the mechanisms associated with the generation of anti-tumor immune responses following immunotherapy.Methods: We report on the design of a microneedle (MN) platform capable of simultaneous delivery of immune activators and collection of interstitial skin fluid (ISF) to monitor therapeutic responses.While either approach has shown promise, the integration of the therapy and diagnostic arms into one MN platform has hardly been explored before.MNs were synthesized out of crosslinked hyaluronic acid (HA) and loaded with a model immunomodulatory nanoparticle-containing drug, CpG oligodinucleotides (TLR9 agonist), for cancer therapy in melanoma and colon cancer models.The therapeutic response was monitored by longitudinal analysis of entrapped immune cells in the MNs following patch retrieval and digestion.Results: Transdermal delivery of CpG-containing NPs with MNs induced anti-tumor immune responses in multiple syngeneic mouse cancer models.CpG-loaded MNs stimulated innate immune cells and reduced tumor growth.Intravital microscopy showed deposition and spatiotemporal co-localization of CpG-NPs within the tumor microenvironment when delivered with MNs.Analysis of MN-sampled ISF revealed similar immune signatures to those seen in the bulk tumor homogenate, such as increased populations of macrophages and effector T cells following treatment.Conclusions: Our hydrogel-based MNs enable effective transdermal drug delivery into immune cells in the tumor microenvironment, and upon retrieval, enable studying the immune response to the therapy over time.This platform has the theranostic potential to deliver a range of combination therapies while detecting biomarkers.
Suppression of breast cancer-associated bone loss with osteoblast proteomes via Hsp90ab1/moesin-mediated inhibition of TGFβ/FN1/CD44 signaling: Erratum
Authors: Xun Sun, Kexin Li, Misato Hase, Rongrong Zha, Yan Feng, Bai-Yan Li, Hiroki Yokota
Journal: Theranostics (2022)

[This corrects the article DOI: 10.7150/thno.66148.].
DNA hypermethylation-induced miR-182 silence targets BCL2 and HOXA9 to facilitate the self-renewal of leukemia stem cell, accelerate acute myeloid leukemia progression, and determine the sensitivity of BCL2 inhibitor venetoclax
Authors: Sisi Ye, Fang Xiong, Xiaofei He, Yigang Yuan, Danyang Li, Daijiao Ye, Liuzhi Shi, Zihan Lin, Min Zhao, Shuya Feng, Bin Zhou, Huachun Weng, Lili Hong, Haige Ye, Shenmeng Gao
Journal: Theranostics (2022)

Rationale: microRNAs (miRNAs) are frequently deregulated and play important roles in the pathogenesis and progression of acute myeloid leukemia (AML). miR-182 functions as an onco-miRNA or tumor suppressor miRNA in the context of different cancers. However, whether miR-182 affects the self-renewal of leukemia stem cells (LSCs) and normal hematopoietic stem progenitor cells (HSPCs) is unknown. Methods: Bisulfite sequencing was used to analyze the methylation status at pri-miR-182 promoter. Lineage-negative HSPCs were isolated from miR-182 knockout (182KO) and wild-type (182WT) mice to construct MLL-AF9-transformed AML model. The effects of miR-182 depletion on the overall survival and function of LSC were analyzed in this mouse model in vivo. Results: miR-182-5p (miR-182) expression was lower in AML blasts than normal controls (NCs) with hypermethylation observed at putative pri-miR-182 promoter in AML blasts but unmethylation in NCs. Overexpression of miR-182 inhibited proliferation, reduced colony formation, and induced apoptosis in leukemic cells. In addition, depletion of miR-182 accelerated the development and shortened the overall survival (OS) in MLL-AF9-transformed murine AML through increasing LSC frequency and self-renewal ability. Consistently, overexpression of miR-182 attenuated AML development and extended the OS in the murine AML model. Most importantly, miR-182 was likely dispensable for normal hematopoiesis. Mechanistically, we identified BCL2 and HOXA9 as two key targets of miR-182 in this context. Most importantly, AML patients with miR-182 unmethylation had high expression of miR-182 followed by low protein expression of BCL2 and resistance to BCL2 inhibitor venetoclax (Ven) in vitro. Conclusions: Our results suggest that miR-182 is a potential therapeutic target for AML patients through attenuating the self-renewal of LSC but not HSPC. miR-182 promoter methylation could determine the sensitivity of Ven treatment and provide a potential biomarker for it.
Engineered biomembrane-derived nanoparticles for nanoscale theranostics
Authors: Ziqing Wu, Hao Zhang, Jing Yan, Yan Wei, Jiacan Su
Journal: Theranostics (2022)

Currently, biological membrane-derived nanoparticles (NPs) have shown enormous potential as drug delivery vehicles due to their outstanding biomimetic properties.To make these NPs more adaptive to complex biological systems, some methods have been developed to modify biomembranes and endow them with more functions while preserving their inherent natures.In this review, we introduce five common approaches used for biomembrane decoration: membrane hybridization, the postinsertion method, chemical methods, metabolism engineering and gene engineering.These methods can functionalize a series of biomembranes derived from red blood cells, white blood cells, tumor cells, platelets, exosomes and so on.Biomembrane engineering could markedly facilitate the targeted drug delivery, treatment and diagnosis of cancer, inflammation, immunological diseases, bone diseases and Alzheimer's disease.It is anticipated that these membrane modification techniques will advance biomembrane-derived NPs into broader applications in the future.
SIRT6-regulated macrophage efferocytosis epigenetically controls inflammation resolution of diabetic periodontitis
Authors: Bang Li, Zhili Xin, Shiyu Gao, Yangjie Li, Songsong Guo, Yu Fu, Rongyao Xu, Dongmiao Wang, Jie Cheng, Laikui Liu, Ping Zhang, Hongbing Jiang
Journal: Theranostics (2022)

Rationale: Diabetes exacerbates the prevalence and severity of periodontitis, leading to severe periodontal destruction and ultimately tooth loss. Delayed resolution of inflammation is a major contributor to diabetic periodontitis (DP) pathogenesis, but the underlying mechanisms of this imbalanced immune homeostasis remain unclear. Methods: We collected periodontium from periodontitis with or without diabetes to confirm the dysfunctional neutrophils and macrophages in aggravated inflammatory damage and impaired inflammation resolution. Our in vitro experiments confirmed that SIRT6 inhibited macrophage efferocytosis by restraining miR-216a-5p-216b-5p-217 cluster maturation through ''non-canonical'' microprocessor complex (RNA pulldown, RIP, immunostaining, CHIP, Luciferase assays, and FISH). Moreover, we constructed m6SKO mice that underwent LIP-induced periodontitis to explore the in vitro and in vivo effect of SIRT6 on macrophage efferocytosis. Finally, antagomiR-217, a miRNA antagonism, was delivered into the periodontium to treat LIP-induced diabetic periodontitis. Results: We discovered that insufficient SIRT6 as a histone deacetylase in macrophages led to unresolved inflammation and aggravated periodontitis in both human and mouse DP with accumulated apoptotic neutrophil (AN) and higher generation of neutrophil extracellular traps. Mechanistically, we validated that macrophage underwent high glucose stimulation resulting in disturbance of the SIRT6-miR-216/217 axis that triggered impeded efferocytosis of AN through targeting the DEL-1/CD36 axis directly. Furthermore, we demonstrated the inhibitory role of SIRT6 for MIR217HG transcription and identified a non-canonical action of microprocessor that SIRT6 epigenetically hindered the splicing of the primary miR-216/217 via the complex of hnRNPA2B1, DGCR8, and Drosha. Notably, by constructing myeloid-specific deletion of SIRT6 mice and locally delivering antagomir-217 in DP models, we strengthened the in vivo effect of this axis in regulating macrophage efferocytosis and inflammation resolution in DP. Conclusions: Our findings delineated the emerging role of SIRT6 in mediating metabolic dysfunction-associated inflammation, and therapeutically targeting this regulatory axis might be a promising strategy for treating diabetes-associated inflammatory diseases.